ArmaGen develops biologics brain amyloid imaging agent for Alzheimer’s disease
The most potent agent for imaging the amyloid plaque in brain of Alzheimer’s disease (AD) is the Abeta(1-40) amyloid peptide. However, the Abeta peptide cannot be developed as a peptide radiopharmaceutical for the in vivoimaging of the amyloid burden in brain, because the peptide does not cross the blood-brain barrier (BBB). The Abeta(1-40) peptide was re-engineered for BBB penetration with a unique 2-vial pharmaceutical approach. ArmaGen’s brain imaging technology combines the molecular Trojan horse technology and avidin-biotin technology with peptide radiopharmaceutical technology. The Abeta(1-40) peptide was synthesized with a single biotin moiety on the amino terminus and an internal tyrosine residue was radiolabeled with 125-iodine. The [N-biotinyl, 125I]-Abeta(1-40) was formulated in one vial. A second vial contained AGT-3 (see Products), which is a genetically engineered IgG-avidin fusion protein, where the IgG domain is an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb acts as a molecular Trojan horse to ferry the attached Abeta peptide radiopharmaceutical across the BBB. The avidin domain of the AGT-3 fusion protein binds with very high affinity to the mono-biotinylated peptide radiopharmaceutical. The stable conjugate of AGT-3 and [N-biotinyl, 125I]-Abeta(1-40), which is designated AGT-3100 (see Products), is formed immediately upon mixing of the 2 vials prior to intravenous administration. AGT-3100 binds selectively to the amyloid plaques in tissue sections of AD brain, as described in the 2012Bioconjugate Chemistry. AGT-3100 can also be modified by conjugation with a chelator groups for radiolabeling with heavy metals suitable for either PET or SPECT external imaging of the brain in humans.